DiabetologiaType 2 DiabetesRCTDecember 19, 2025

Effects of combined intraduodenal administration of lauric acid and L-tryptophan on postprandial plasma glucose, glucoregulatory hormones and gastric emptying in type 2 diabetes: a double-blind, randomised, crossover study.

Anjom-Shoae J, Fitzgerald PCE, Rose BD, Bitarafan V, Rehfeld JF, Horowitz M, Feinle-Bisset C

View on PubMed DOI: 10.1007/s00125-025-06630-0

Key Finding

Combining two nutrients (lauric acid and L-tryptophan) delivered directly into the small intestine reduced peak blood sugar by 1.3 mmol/L in men with type 2 diabetes by slowing stomach emptying and boosting gut hormones.

What This Study Found

Think of your stomach as a dam controlling the flow of food into your small intestine. This study tested whether two specific nutrients - lauric acid (found in coconut oil) and L-tryptophan (an amino acid) - could act like 'traffic controllers' when delivered directly past the stomach into the small intestine. The researchers gave 11 men with type 2 diabetes these nutrients through a tube, then had them drink a meal replacement shake. Like a perfectly timed relay race, the combination of these two nutrients triggered the release of hormones (GLP-1 and CCK) that told the stomach to slow down its emptying - essentially making the 'dam' release food more gradually. This slower, controlled release meant blood sugar didn't spike as dramatically after eating. Interestingly, neither nutrient worked alone - they needed each other to be effective, like two keys required to open a safety deposit box.

Statistics Decoded

Peak blood sugar dropped from 11.1 mmol/L (control) to 9.8 mmol/L (combination treatment) - that's a 12% reduction in the highest blood sugar spike. The p=0.01 means there was only a 1% chance this difference happened by luck - like correctly guessing heads on a coin flip 7 times in a row. The p=0.02 for 'overall' glucose means the combination also kept blood sugar lower throughout the entire 3-hour measurement period, with just a 2% chance this was coincidence. The gastric emptying result (p=0.001) means there was less than a 0.1% chance the slower stomach emptying was random - essentially a statistical certainty.

Why This Matters

This opens a new avenue for managing type 2 diabetes through natural nutrients rather than just medications, potentially offering a gentler approach to controlling blood sugar spikes after meals. The fact that tiny amounts of common nutrients can significantly impact glucose control suggests we might develop food-based therapies or functional foods for diabetes management.

Original Abstract

In healthy men, lauric acid (C12) and L-tryptophan (Trp), when administered intraduodenally in loads of 1.26 and 0.42 kJ/min (0.3 and 0.1 kcal/min), respectively, that are individually ineffective, stimulate glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK), when combined. Both hormones slow gastric emptying, suppress energy intake and lower postprandial glucose. We have now investigated the hypothesis that combined intraduodenal administration of these nutrients reduces postprandial glucose in type 2 diabetes. In a randomised, blinded (investigators and participants), crossover study performed in the University of Adelaide Clinical Research Facility, 11 men with type 2 diabetes (age: 69 ± 7 years; HbA1c: 51 ± 5 mmol/mol [6.8 ± 0.3%]; BMI: 28 ± 1 kg/m2), each received, on four separate occasions, 45 min intraduodenal infusions of C12 (1.26 kJ/min), Trp (0.42 kJ/min), C12+Trp (1.68 kJ/min), or 0.9% saline (control), 30 min before a mixed-nutrient drink (350 ml, 2092 kJ (500 kcal), 74 g carbohydrate) containing 100 mg 13C-acetate. Plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and CCK concentrations were measured at baseline, following treatments alone, and for 180 min post-drink. Gastric emptying was assessed via 13C-acetate breath test. C12+Trp, but not C12 or Trp, reduced overall (p=0.02) and peak (mmol/l; control: 11.1 ± 0.6, Trp: 10.3 ± 0.5, C12: 10.7 ± 0.6, C12+Trp: 9.8 ± 0.5; p=0.01) plasma glucose. C12+Trp slowed gastric emptying (p=0.001), and increased pre-drink plasma GLP-1, GIP and CCK (all p<0.05), without affecting insulin or C-peptide. No treatment effects were observed postprandially. In type 2 diabetes, intraduodenal C12+Trp lowers postprandial glucose, probably primarily by slowing of gastric emptying and mediated by GLP-1 and CCK. These findings support further exploration of nutrient-based gastrointestinal strategies to optimise glycaemic management in type 2 diabetes. Australian New Zealand Clinical Trials Registry ( www.anzctr.org.au ) ACTRN12623000778684 FUNDING: JAS and VB were each supported by Adelaide Scholarship International stipends, provided by the University of Adelaide (JAS, 2021-2025; VB, 2017-2020) and CFB by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (Grant 1103020, 2016-2023). The research was supported by a Diabetes Australia Research Project Grant (2021-2022) to CFB.